Investigators have assessed whether RNAs can be used as a biomarker to predict which patients with stage II colorectal cancer may benefit from postsurgical chemotherapy, according to a recent study published by Korsgaard et al in The American Journal of Pathology.
Background
Colorectal cancer is the third most common and second most deadly cancer type across the world—with more than 1 million new cases and more than 500,000 estimated cancer-related deaths per year. A considerable number of patients with locally advanced disease experience cancer recurrence.
Stage II colorectal cancer is defined as having penetrated the bowel wall but without lymph node metastases or distant metastases at the time of diagnosis. The decision to treat these patients with adjuvant chemotherapy remains controversial. Therefore, there is an urgent need to identify reliable prognostic biomarkers in this setting.
“There are currently no reliable biomarkers for determining whether [patients with] stage II [colorectal] cancer would benefit from adjuvant chemotherapy following surgery. Identification of new risk-stratification biomarkers is beneficial; it may spare many patients who are actually cured by the surgery from toxic side effects of chemotherapy while still selecting patients who would benefit from it,” emphasized senior study author Lasse Sommer Kristensen, PhD, of the Department of Biomedicine at Aarhus University.
Study Methods and Results
In this study, the investigators used total RNA sequencing to profile the landscape and differential expression of coding RNA, linear noncoding RNA, and circular RNA in patients who had stage II colorectal cancer with and without disease recurrence as well as in patients with stage III colorectal cancer. They also profiled adjacent normal tissues and liver metastases.
The investigators subsequently evaluated the biomarker potential of differentially expressed RNAs in stage II colorectal cancer. They examined patient data—age, sex, date of surgery, chemotherapy, tumor location, and date of recurrence—as well as histopathologic data such as staging status, histologic subtype, tumor differentiation, mismatch repair status, and mutational analysis collected through the Danish Pathology Registry (Patobank).
The investigators noted that 62 samples from 52 patients were included in the analysis: 18 from patients with stage II colorectal cancer without recurrence, 10 from patients with stage II colorectal cancer with recurrence, 8 from patients with stage III colorectal cancer with recurrence, 16 from liver metastases, 6 from adjacent normal colon tissues, and 4 from adjacent normal liver tissues.
They discovered that RNAs with housekeeping functions such as small nuclear RNAs, small nucleolar RNAs, and small Cajal body–specific RNAs were globally upregulated in patients with stage II colorectal cancer who experienced cancer recurrence compared with those who did not experience cancer recurrence. The investigators indicated that housekeeping RNAs are constitutively expressed and mostly involved in RNA splicing regulation and RNA modification.
Conclusions
The findings may have unveiled numerous differentially expressed RNAs across various classes between recurrent and nonrecurrent colorectal cancers. The expression of these RNA classes was found to be retained in liver metastases, suggesting they may play a critical role in the metastatic process.
“We were the first to profile many different types of RNA in [patients with] stage II [colorectal] cancer with different outcomes and discovered novel individual biomarkers as well as entire classes of RNA that are commonly deregulated in patients with poor outcomes. Furthermore, many of these classes of RNAs showed great prognostic potential to assist treatment decisions in stage II [colorectal] cancer that should be validated in larger groups of patients,” Dr. Kristensen concluded.
Disclosure: The research in this study was supported by the Lundbeck Foundation, Riisfort Fonden, Magda Sofie Og Aase Lütz’s Mindelegat Fond, the Novo Nordisk Foundation ODIN program, the Danish Cancer Society, the Region of Southern Denmark, the Research Council at Lillebaelt Hospital, and Købmand i Odense Johann og Hanne Weimann Født Seedorffs Legat. For full disclosures of the study authors, visit ajp.amjpathol.org.
